NSCLCPhase 1NCT02607813
Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations
A Phase 1 study testing LXH254 and PDR001 in people with NSCLC and Ovarian Cancer, run by Novartis Pharmaceuticals at 18 sites in 10 countries.
Trial summary
A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Ovarian Cancer, Melanoma
- What is being tested?
- LXH254 and PDR001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 142 participants
- Where
- 18 sitesin 10 countries
- Study dates
- 18 Jan 2016to 19 Feb 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Presence of at least one measurable lesion according to RECIST v1.1.
- Documented MAPK alteration
- Additional inclusion criteria for the Dose Expansion part: LXH254 in combination with PDR001:
- Patients with confirmed KRAS-mutated NSCLC
- Patients with confirmed NRAS-mutated melanoma (cutaneous melanoma only)
Who cannot join
- Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled in the dose expansion part.
- Exceptions may be made after documented agreement between Novartis and Investigator.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- Patients receiving proton pump inhibitors which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
- Pregnant or nursing (lactating) women
Show all 15Show fewer
- Additional exclusion criteria for LXH254 in combination with PDR001
- History of severe hypersensitivity reactions, which in the opinion of the investigator may cause in increased risk of serious infusion reaction.
- Known human immunodeficiency virus (HIV).
- Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection.
- Active, known or suspected autoimmune disease.
- Active infection requiring systemic antibiotic therapy
- Patients requiring systemic steroid therapy or any immunosuppressive therapy (≥10mg/day prednisone or equivalent) which cannot be discontinued at least 7 days prior to first dose of study treatment.
- Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment.
- Other inclusion/exclusion criteria as per protocol may apply.
Trial locations and contacts
18 sites in 10 countries.
18 sites in 10 countries
United States3 sites
Massachusetts General Hospital MGH Cancer Center
Boston, Massachusetts, 02114
UT M.D Anderson Cancer Center SC - LXH254X2101
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center SC - LXH254X2101
New York, New York, 10065
Italy3 sites
Novartis Investigative Site
Milan, MI, 20133
Novartis Investigative Site
Modena, MO, 41124
Novartis Investigative Site
Naples, 80131
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28046
France2 sites
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Toulouse, 31059
Netherlands2 sites
Novartis Investigative Site
Groningen, 9713 GZ
Medical Oncology, Erasmus MC
Rotterdam, 3075 CE
About this study
Official title: A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations
A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.
- Conditions
- NSCLC, Ovarian Cancer, Melanoma, Other Solid Tumors
- Being tested
- LXH254, PDR001
- Keywords
- LXH254, CRAF, MAPK, solid tumor, PDR001
- Medical subject headings
- Ovarian Neoplasms, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LXH254Drug
pan-RAF inhibitor
PDR001Drug
Biological: PDR001 anti-PD1 antibody
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation LXH254 | Experimental | Not described Receives: Drug: LXH254 |
| Dose expansion LXH254: Group 1 | Experimental | Not described Receives: Drug: LXH254 |
| Dose expansion LXH254: Group 2 | Experimental | Not described Receives: Drug: LXH254 |
| Dose expansion LXH254: Group 3 | Experimental | Not described Receives: Drug: LXH254 |
| Dose expansion: LXH254 + PDR001 | Experimental | Not described Receives: Drug: LXH254; Drug: PDR001 |
| Dose escalation LXH254 + PDR001 | Experimental | Not described Receives: Drug: LXH254; Drug: PDR001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity.
cycle = 28 days
Measured: From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only)
cycle = 28 days
Measured: 28 days
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only)
cycle =28 days
Measured: 56 days
Secondary outcomes (16)
Overall response rate (ORR)
cycle = 28 days
Measured: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Disease control rate (DCR)
cycle = 28 days
Measured: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Duration of response (DoR)
cycle = 28 days
Measured: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Progression-free survival (PFS)
cycle = 28 days
Measured: Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months
Overall survival (OS) - only for dose expansion
cycle = 28 days
Measured: From time of start treatment until the date of death; expected duration approximately 12 months
Plasma concentrations of LXH254
cycle = 28 days
Measured: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: Area Under the Curve (AUC)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: Peak Plasma Concentration (Cmax)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: Time to Peak Plasma Concentration (Tmax)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: half-life (T1/2)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor tissue and in blood
cycle = 28 days
Measured: Cycle 1 day 1, 2, 3, 15, and 16; upon disease progression (expected duration approximately 12 months)
Plasma concentrations of PDR001
cycle = 28 days
Measured: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: Area Under the Curve (AUC)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: Peak Plasma Concentration (Cmax)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: Time to Peak Plasma Concentration (Tmax)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: half-life (T1/2)
cycle = 28 days
Measured: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2015 (estimated)
- Study start18 Jan 2016
- Primary completion18 Feb 2022
- Study completion19 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NSCLCStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02607813
- Sponsor's protocol ID
- CLXH254X2101
- Other IDs
- 2015-003421-33, 2015
- Status last verified
- Mar 2022
- First submitted
- 5 Nov 2015
- Last updated
- 21 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Finding Study of Oral LXH254 in Adult Patients With Advanced Solid Tumors Harboring MAPK Pathway Alterations
- ClinicalTrials.gov ID
- NCT02607813
- Acronym / sponsor ID
- CLXH254X2101
- Conditions
- NSCLC, Ovarian Cancer, Melanoma, Other Solid Tumors
- Keywords
- LXH254, CRAF, MAPK, solid tumor, PDR001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 142 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 18 Jan 2016 (actual)
- Primary completion
- 18 Feb 2022 (actual)
- Study completion
- 19 Feb 2022 (actual)
- First posted
- 18 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase I Study of LXH254 in Patients With Advanced Solid Tumors That Harbor MAPK Pathway Alterations.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Dose escalation LXH254 | Experimental | Drug: LXH254 |
| Dose expansion LXH254: Group 1 | Experimental | Drug: LXH254 |
| Dose expansion LXH254: Group 2 | Experimental | Drug: LXH254 |
| Dose expansion LXH254: Group 3 | Experimental | Drug: LXH254 |
| Dose expansion: LXH254 + PDR001 | Experimental | Drug: LXH254, Drug: PDR001 |
| Dose escalation LXH254 + PDR001 | Experimental | Drug: LXH254, Drug: PDR001 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- All patients participating in this clinical trial must have progressed following standard therapy, or for whom, in the opinion of the Investigator, no effective standard therapy exists, is tolerated or appropriate.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- Presence of at least one measurable lesion according to RECIST v1.1.
- Documented MAPK alteration
- Additional inclusion criteria for the Dose Expansion part: LXH254 in combination with PDR001:
Key exclusion criteria (15 listed)
- Prior treatment with a BRAFi, MEKi and/or pan-RAF inihibitors for patients to be enrolled in the dose expansion part.
- Exceptions may be made after documented agreement between Novartis and Investigator.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
- Patients receiving proton pump inhibitors which cannot be discontinued 3 days prior to the start study treatment and for the duration of the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LXH254pan-RAF inhibitor | Drug | Dose escalation LXH254, Dose escalation LXH254 + PDR001, Dose expansion LXH254: Group 1, Dose expansion LXH254: Group 2, Dose expansion LXH254: Group 3, Dose expansion: LXH254 + PDR001 |
| PDR001Biological: PDR001 anti-PD1 antibody | Drug | Dose escalation LXH254 + PDR001, Dose expansion: LXH254 + PDR001 |
Primary outcome
Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity.
Time frame: From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)
cycle = 28 days
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 single agent only)
Time frame: 28 days
cycle = 28 days
Incidence and nature of dose limiting toxicities (DLTs) (dose escalation and LXH254 in combination with PDR001 only)
Time frame: 56 days
cycle =28 days
16 secondary outcomes
Overall response rate (ORR)
Time frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Disease control rate (DCR)
Time frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Duration of response (DoR)
Time frame: Every 2 cycles after starting study treatment until end of treatment; expected duration approximately 12 months
Progression-free survival (PFS)
Time frame: Every 2 cycles after starting study treatment until disease progression; expected duration approximately 12 months
Overall survival (OS) - only for dose expansion
Time frame: From time of start treatment until the date of death; expected duration approximately 12 months
Plasma concentrations of LXH254
Time frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: Area Under the Curve (AUC)
Time frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: Peak Plasma Concentration (Cmax)
Time frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: Time to Peak Plasma Concentration (Tmax)
Time frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Derived PK parameters of LXH254: half-life (T1/2)
Time frame: Cycle 1 days 1, 2, 3, 8, 15, and 16; Cycle 2 days 1 and 15; Cycle 3 Day 1; Cycle 5 Day 1
Changes from baseline of pharmacodynamics (PD) marker DUSP6 in tumor tissue and in blood
Time frame: Cycle 1 day 1, 2, 3, 15, and 16; upon disease progression (expected duration approximately 12 months)
Plasma concentrations of PDR001
Time frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: Area Under the Curve (AUC)
Time frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: Peak Plasma Concentration (Cmax)
Time frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: Time to Peak Plasma Concentration (Tmax)
Time frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Derived PK parameters of PDR001: half-life (T1/2)
Time frame: Cycle 1 days 1, 2, 8, and 15; Cycle 2 days 1; Cycle 3 Day 1, 2 and 8; Cycle 4 Day 1; Cycle 5 Day 1; Cycle 6 Day 1
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Dec 2022.
- Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
18 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LXH254 and PDR001 in people with NSCLC and Ovarian Cancer, run by Novartis Pharmaceuticals at 18 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Italy, Spain, France, Netherlands and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability as assessed by incidence and severity of adverse events (AEs), dose interruptions, reductions, and dose intensity. (time frame: From Cycle 1 Day 1 until 30 days for LXH254 single agent and 150 days for LXH254 in combination with PDR001 post study treatment (expected duration approximately 12 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Dec 2022.